Many fungal and bacterial pathogens produce proteolytic enzymes that facilitate penetration into fish skin or eggshells. These diseases are a major and growing challenge to sustainable aquaculture in the United States. Our Phase I research results demonstrated the feasibility of new, non-toxic, disease prevention and treatment strategies. The key is our focus on safe, natural materials combined with innovative delivery systems. We propose to enhance the efficacy of the treatments identified in Phase I by applying recent advances in particle chemistry and nanotechnology. First, we will examine the efficacy of our latest formulation discoveries against an array of pathogenic Saprolegnia fungi from diverse geographic areas to validate their widespread applicability. Second, we will examine unique enzyme systems and test for anti-fungal activity. Third, we will work to magnify the therapeutic potency of our formulations by combining them to non-toxic micro- or nanoparticles. Fourth, these treatment systems will be tested in catfish and trout for safety and efficacy. Lastly, this agriculturally-related manufacturing technology will be commercialized by developing initial prototype products and field testing them in conjunction with ProFishent's Phase III collaborator, AquaTactics, LLC. These treatments should promote an expansion of the number of cultured species, make the harvest volume more predictable, and increase the productivity of private and public sector aquaculture in the U.S.A.